Brexpiprazole

Summary

Brexpiprazole (CHEMBL2105760) is an approved small molecule (ATC N05AX16) targeting DRD2; indicated across 14 conditions including psychotic disorder and schizoaffective disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AX16
• Targets: 1 (DRD2)
• Indications: 14 conditions
• Clinical trials: 82
• Chemistry: 433.6 Da · C25H27N3O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2105760
Name	Brexpiprazole
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11978813
ATC	N05AX16
Molecular formula	C25H27N3O2S
Molecular weight	433.6
InChIKey	ZKIAIYBUSXZPLP-UHFFFAOYSA-N

SMILES: C1CN(CCN1CCCCOC2=CC3=C(C=C2)C=CC(=O)N3)C4=C5C=CSC5=CC=C4

IUPAC name: 7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-1H-quinolin-2-one

Also known as: Brexpiprazol, Brexpiprazole, OPC-34712, Rexulti, Rxulti, BREXPIPRAZOLE, US9206167, 1

Patent coverage: 732 distinct patent families (1,755 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 1,465 (83%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DRD2	D2 receptor	Partial agonist	9.52	0%	P14416

Broader ChEMBL bioactivity targets: 35 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, D(1B) dopamine receptor, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, 5-hydroxytryptamine receptor 1D, D(1A) dopamine receptor, Beta-2 adrenergic receptor.

Bioactivity

ChEMBL activities: 50 potent at pChembl ≥ 5 of 50 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P19327	10.05	Ki	0.09	nM	CHEMBL_ACT_18858922
HTR1A	9.92	Ki	0.12	nM	CHEMBL_ACT_18891603
HTR1A	9.92	Ki	0.12	nM	CHEMBL_ACT_22792231
P61169	9.7	Ki	0.2	nM	CHEMBL_ACT_17723665
DRD2	9.52	Ki	0.3	nM	CHEMBL_ACT_18891553
DRD2	9.52	Ki	0.3	nM	CHEMBL_ACT_22792232
HTR2B	9.4	Ki	0.4	nM	CHEMBL_ACT_18891417
HTR2A	9.33	Ki	0.47	nM	CHEMBL_ACT_18891565
HTR2A	9.33	Ki	0.47	nM	CHEMBL_ACT_22792233
DRD2	9.29	Ki	0.51	nM	CHEMBL_ACT_23301285
DRD2	9.29	Ki	0.51	nM	CHEMBL_ACT_23301286
P14842	8.64	Ki	2.3	nM	CHEMBL_ACT_17723725
HTR7	8.43	Ki	3.7	nM	CHEMBL_ACT_18891534
P61169	8.42	Ki	3.8	nM	CHEMBL_ACT_18858921
DRD2	8.22	Ki	5.99	nM	CHEMBL_ACT_25741506
DRD2	8.2	EC50	6.3	nM	CHEMBL_ACT_20667761
HRH1	8.05	Ki	8.88	nM	CHEMBL_ACT_25741510
DRD2	8	EC50	10	nM	CHEMBL_ACT_23301382
DRD2	7.99	EC50	10.2	nM	CHEMBL_ACT_23301381
DRD3	7.98	Ki	10.42	nM	CHEMBL_ACT_25741507
DRD2	7.79	EC50	16.1	nM	CHEMBL_ACT_23301519
DRD2	7.79	EC50	16.22	nM	CHEMBL_ACT_23301520
HTR2A	7.74	Ki	18.26	nM	CHEMBL_ACT_25741516
HTR1A	7.63	Ki	23.24	nM	CHEMBL_ACT_25741512
HTR1D	7.62	Ki	24.05	nM	CHEMBL_ACT_25741514
ADRA1A	7.53	Ki	29.27	nM	CHEMBL_ACT_25741497
HTR7	7.52	Ki	30.43	nM	CHEMBL_ACT_25741521
DRD4	7.44	Ki	35.98	nM	CHEMBL_ACT_25741508
DRD1	7.43	Ki	37.46	nM	CHEMBL_ACT_25741505
HTR1B	7.37	Ki	42.64	nM	CHEMBL_ACT_25741513

Target pathways

Aggregated over 1 target gene(s): DRD2.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Dopamine receptors	1	DRD2

Dominant GO biological processes

GO term	Targets
temperature homeostasis	1
response to hypoxia	1
response to amphetamine	1
nervous system process involved in regulation of systemic arterial blood pressure	1
regulation of heart rate	1
regulation of sodium ion transport	1
G protein-coupled receptor internalization	1
positive regulation of neuroblast proliferation	1
positive regulation of receptor internalization	1
intracellular calcium ion homeostasis	1
autophagy	1
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuron-neuron synaptic transmission	1
neuroblast proliferation	1

Indications & clinical

Indications

14 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
psychotic disorder	4	MONDO:0005485	EFO:0005407
schizoaffective disorder	4	MONDO:0005487	EFO:0005411
major depressive disorder	4	MONDO:0002009	MONDO:0002009
post-traumatic stress disorder	3	MONDO:0005146	EFO:0001358
sleep disorder	3	MONDO:0100081	EFO:0008568
depressive disorder	3	MONDO:0002050	MONDO:0002050
bipolar disorder	3	MONDO:0004985	EFO:0009963
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
mental disorder	3	MONDO:0005084	EFO:0000677
borderline personality disorder	2	MONDO:0001156	HP:0012076
alcohol abuse	2	MONDO:0002046	MONDO:0007079

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 82.

Phase distribution

Phase	Trials
PHASE3	46
PHASE2	11
PHASE1	11
PHASE4	6
PHASE2/PHASE3	4
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05017311	PHASE4	RECRUITING	Optimized Predictive Treatment In Medications for Unipolar Major Depression (OPTIMUM-D)
NCT03149991	PHASE4	COMPLETED	A Study of Brexpiprazole Plus Ketamine in Treatment-Resistant Depression (TRD)
NCT03427892	PHASE4	COMPLETED	Brexpiprazole for Bipolar Depression
NCT03526354	PHASE4	COMPLETED	Controlled Trial of Brexpiprazole For The Treatment of Co-occurring Schizophrenia and Substance Use Disorder
NCT04830215	PHASE4	COMPLETED	Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder
NCT05504486	PHASE4	WITHDRAWN	Open-label Brexpiprazole fMRI Trial in Adults With Major Depressive Disorder and Anxiety
NCT04569448	PHASE3	RECRUITING	Brexpiprazole Treatment for Bipolar I Depression
NCT01360632	PHASE3	COMPLETED	Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)
NCT01360645	PHASE3	COMPLETED	Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial)
NCT01360866	PHASE3	COMPLETED	Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder (the Orion Trial)
NCT01393613	PHASE3	COMPLETED	Efficacy Study of OPC-34712 in Adults With Acute Schizophrenia
NCT01397786	PHASE3	COMPLETED	Safety and Tolerability Study of Oral OPC-34712 as Maintenance Treatment in Adults With Schizophrenia
NCT01451164	PHASE2/PHASE3	COMPLETED	A Dose-finding Trial of OPC-34712 in Patients With Schizophrenia
NCT01456897	PHASE3	COMPLETED	A Long-term Trial of OPC-34712 in Patients With Schizophrenia
NCT01668797	PHASE3	COMPLETED	Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia
NCT01727726	PHASE3	COMPLETED	A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
NCT01810380	PHASE3	COMPLETED	Brexpiprazole in Patients With Acute Schizophrenia
NCT01810783	PHASE3	COMPLETED	Brexpiprazole in Patients With Schizophrenia
NCT01837797	PHASE3	TERMINATED	Efficacy and Safety of Brexpiprazole as Adjunctive Treatment in Elderly Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
NCT01838681	PHASE3	COMPLETED	Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
NCT01862640	PHASE3	COMPLETED	A Phase 3, 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of 2 Fixed Doses of Brexpiprazole in the Treatment of Alzheimer’s Agitation
NCT01922258	PHASE3	COMPLETED	Safety and Tolerability Study of Flexible Dosing of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer’s Type
NCT01942733	PHASE3	COMPLETED	Study of Brexpiprazole as Adjunctive Treatment of Sleep Disturbances in Patients With Major Depressive Disorder
NCT01942785	PHASE3	COMPLETED	Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy
NCT01944969	PHASE3	TERMINATED	Long-term Safety and Tolerability Study of Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder
NCT01987960	PHASE3	TERMINATED	Brexpiprazole as an Adjunctive Treatment to Paroxetine or Sertraline in Adult Patients Suffering From Post-traumatic Stress Disorder (PTSD)
NCT02012218	PHASE3	COMPLETED	Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy
NCT02013531	PHASE3	COMPLETED	Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Adults With Major Depressive Disorder and Anxiety Symptoms
NCT02013609	PHASE3	COMPLETED	Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Active Adults, 18 to 35 Years Old, With Major Depressive Disorder Who Are in a School or Work Environment
NCT02013622	PHASE3	COMPLETED	Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Early-Episode Schizophrenia
NCT02054702	PHASE3	COMPLETED	Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia
NCT02194933	PHASE3	COMPLETED	Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Schizophrenia With Impulsivity
NCT02196506	PHASE3	COMPLETED	Study of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress
NCT02212613	PHASE3	WITHDRAWN	Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability
NCT02400346	PHASE3	COMPLETED	Evaluation of the Safety of Adjunct Brexpiprazole in Elderly Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Treatment
NCT02758067	PHASE3	WITHDRAWN	Comparison of the Effectiveness of Brexpiprazole With That of Risperidone
NCT03198078	PHASE3	COMPLETED	Trial to Evaluate the Short-term Safety & Efficacy of Brexpiprazole Monotherapy in the Treatment of Adolescents With Schizophrenia
NCT03238326	PHASE3	COMPLETED	Safety and Tolerability of Open-Label Flexible-dose Brexpiprazole as Maintenance Treatment in Adolescents With Schizophrenia
NCT03257865	PHASE3	COMPLETED	A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder
NCT03259555	PHASE3	COMPLETED	A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for brexpiprazole and CYP2D6	DPWG	CYP2D6	yes	yes

PharmGKB also curates 1 clinical and 8 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

296 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2
AMISULPRIDE	ChEMBL	Phase 4 (approved)	DRD2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2
AMLODIPINE	ChEMBL	Phase 4 (approved)	DRD2
AMODIAQUINE	ChEMBL	Phase 4 (approved)	DRD2
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2
AMSACRINE	ChEMBL	Phase 4 (approved)	DRD2
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	DRD2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2
ARMODAFINIL	ChEMBL	Phase 4 (approved)	DRD2
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2
AZATADINE	ChEMBL	Phase 4 (approved)	DRD2
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	DRD2
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	DRD2
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2
BEPRIDIL	ChEMBL	Phase 4 (approved)	DRD2
BETAMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	DRD2
BLONANSERIN	ChEMBL	Phase 4 (approved)	DRD2
BOSUTINIB	ChEMBL	Phase 4 (approved)	DRD2
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD2
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2
CANNABIDIOL	ChEMBL	Phase 4 (approved)	DRD2
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2
CEFEPIME	ChEMBL	Phase 4 (approved)	DRD2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	DRD2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	DRD2
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2
CLOFAZIMINE	ChEMBL	Phase 4 (approved)	DRD2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	DRD2
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2
DACOMITINIB	ChEMBL	Phase 4 (approved)	DRD2
DARIFENACIN	ChEMBL	Phase 4 (approved)	DRD2
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	DRD2
DESIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2
DESLORATADINE	ChEMBL	Phase 4 (approved)	DRD2
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	DRD2
DIPHENIDOL	ChEMBL	Phase 4 (approved)	DRD2
DISULFIRAM	ChEMBL	Phase 4 (approved)	DRD2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	DRD2
DOMPERIDONE	ChEMBL	Phase 4 (approved)	DRD2
DOPAMINE	ChEMBL	Phase 4 (approved)	DRD2
DOTHIEPIN	ChEMBL	Phase 4 (approved)	DRD2